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Record W3010451509 · doi:10.1074/mcp.ra119.001910

Discovery of a Redox Thiol Switch: Implications for Cellular Energy Metabolism

2020· article· en· W3010451509 on OpenAlexaff
Xing‐Huang Gao, Ling Li, Marc Parisien, Jing Wu, Ilya Bederman, Zhaofeng Gao, Dawid Krokowski, Steven M. Chirieleison, Derek W. Abbott, Benlian Wang, Peter Arvan, Mark J. Cameron, Mark R. Chance, Belinda Willard, Maria Hatzoglou

Bibliographic record

VenueMolecular & Cellular Proteomics · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSulfur Compounds in Biology
Canadian institutionsMcGill University Health Centre
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesNarodowym Centrum NaukiNational Institutes of HealthNational Center for Research ResourcesAmerican Diabetes Association
KeywordsThiolEnergy metabolismRedoxChemistryMetabolismBiophysicsBiochemistryBiologyInorganic chemistry

Abstract

fetched live from OpenAlex

The redox-based modifications of cysteine residues in proteins regulate their function in many biological processes. The gas molecule H 2 S has been shown to persulfidate redox sensitive cysteine residues resulting in an H 2 S-modified proteome known as the sulfhydrome. Tandem Mass Tags (TMT) multiplexing strategies for large-scale proteomic analyses have become increasingly prevalent in detecting cysteine modifications. Here we developed a TMT-based proteomics approach for selectively trapping and tagging cysteine persulfides in the cellular proteomes. We revealed the natural protein sulfhydrome of two human cell lines, and identified insulin as a novel substrate in pancreatic beta cells. Moreover, we showed that under oxidative stress conditions, increased H 2 S can target enzymes involved in energy metabolism by switching specific cysteine modifications to persulfides. Specifically, we discovered a Redox Thiol Switch, from protein S-glutathioinylation to S-persulfidation (RTS GS ). We propose that the RTS GS from S-glutathioinylation to S-persulfidation is a potential mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.235
Teacher spread0.220 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations45
Published2020
Admission routes1
Has abstractyes

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